Metagenomic analysis reveals unexplored diversity of archaeal virome in the human gut

Abstract The human gut microbiome has been extensively explored, while the archaeal viruses remain largely unknown. Here, we conducted a comprehensive analysis to identify human gut archaeal virus sequences in 3,971 assembled metagenomes and the existing human gut virus collections using the CRISPR spacer and viral signature-based approach. This resulted in 1,279 archaeal viral species, of which, 95.2% infected Methanobrevibacteria_A, 85.1% were not found in existing virus collections, 43.5% shared identity < 95% with the proviruses in the UHGG archaeal genomes, 37.2% had a host range spanning > 2 archaeal species, and 55.7% were highly prevalent in > 1% of the human population. Besides viral hallmark genes, the archaeal viral genetic repertoire includes a methanogenic archaeal virus-specific gene peiW that frequently occurred in the viral sequences (n = 150). The analysis of 33 complete caudoviral genomes often discovered the genes (integrase,n = 29; MazE, n = 10) regulating the viral lysogenic-lytic cycle, demonstrating that the temperate viruses likely predominate in the human gut archaeal virome. Together, our work uncovers the considerable unexplored diversity of the human gut archaeal viruses, revealing the novel and unexpected facet of the human gut microbiome.